September 29, 2010 (NOT-OD-11-007) - NIH to Require Use of Updated Electronic Application Forms in 2011. Adobe B1 forms are required for due dates on or after May 8, 2011.

August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections
must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

June 22, 2010 - See Notice NOT-AR-10-039 The purpose of this notice is to extend the second receipt date.

June 18, 2010 - See Notice NOT-AR-10-040 The purpose of this notice is to announce an increase in the budget limit for applications submitted in response to this PAR.

December 7, 2009 -
This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions.

Program
Announcement (PA) Number: PAR-09-135

NOTICE: Applications submitted
in response to this Funding Opportunity Announcement (FOA) for Federal
assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424
Research and Related (R&R) forms and the SF424 (R&R) Application
Guide.

APPLICATIONS MAY NOT
BE SUBMITTED IN PAPER FORMAT.

This FOA must be read
in conjunction with the application guidelines included with this announcement
in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A registration process
is necessary before submission and applicants are highly encouraged to start
the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)93.846

Key DatesRelease/Posted Date: March 20, 2009
Opening Date: August
29, 2009 (Earliest date
an application may be submitted to Grants.gov)Letters of Intent Receipt Date(s): August
31, 2009; June 1, 2010; June 1, 2011 NOTE: On-time submission requires that
applications be successfully submitted to Grants.gov no later than 5:00 p.m.
local time (of the applicant institution/organization). Application Due Date(s): September 29, 2009; June 29, 2010 (Changed to July 27, 2010 per NOT-AR-10-039); June 29, 2011Peer Review
Date(s): February/March 2010, October/November
2010, October/November 2011Council Review
Date(s):May
2010, January 2011, January 2012 Earliest
Anticipated Start Date(s):July 2010, April 2011, April 2012 Additional Information To Be Available
Date (Activation Date):Not ApplicableExpiration Date: June
30, 2011

Due Dates for E.O. 12372

Not Applicable

Additional
Overview Content

Executive Summary

Purpose.This Funding
Opportunity Announcement (FOA), issued by the National Institute of
Arthritis and Musculoskeletal and Skin Diseases, National Institutes of
Health, encourages applications that propose to perform replication,
fine-mapping, and sequencing studies of human genomic regions that are
putatively associated with phenotypes relevant to the NIAMS mission.
Genomic regions of interest are primarily those identified by genome-wide
association studies (GWAS). The objective of this FOA is to enhance the
identification of causal genes and genetic variants that influence complex
diseases relevant to the NIAMS mission. Replication, fine-mapping, and
sequencing studies are to be conducted in existing cohorts with defined
phenotypes. This FOA will not support recruitment of human subjects,
collection of medical or phenotypic data, studies using animal models, or
the initial discovery phase of GWAS.

Mechanism
of Support.This FOA will
utilize the NIH Research Project (R01) grant mechanism. In some instances, an active NIAMS R01 award may currently
support a GWAS with a two-stage design, including initial discovery and
replication. In such instances, investigators may submit a revision
(formerly competing supplement) application in response to this FOA, to
support additional replication, fine-mapping, or sequencing efforts,
provided the application conforms to both the budgetary requirements of
this FOA and the format requirements of revision applications.

Funds Available and Anticipated Number of Awards. For
this funding opportunity, the NIAMS expects to commit
approximately $1.5 million total costs in each of fiscal years 2010, 2011, and
2012, to support three to four new projects per year. Budgets up to $250,000
direct costs per year and project periods of up to two years may be requested. Awards issued under this FOA are contingent upon the
availability of funds and the submission of a sufficient number of meritorious
applications.

Budget and Project Period.Applications
may request direct costs up to $250,000 per year and project duration of
up to two years.

Eligible Project Directors/Principal Investigators
(PDs/PIs).Individuals
with the skills, knowledge, and resources necessary to carry out the proposed
research are invited to work with their institution/organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.

Number
of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the
application.

Number of Applications. Applicants may submit more than one application,
provided that each application is scientifically distinct.

Resubmissions.Applicants
may submit a resubmission application, but such application must include an
Introduction addressing the previous peer review critique (Summary Statement). See
new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).

Renewals.Renewal
(formerly competing continuation) applications will not be accepted for this
FOA.

Application
Materials.SeeSection IV.1for application materials.All applications, including resubmission, revision and renewal, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions.

General Information.For
general information on SF424 (R&R) Application and Electronic Submission,
see these Web sites:

This Funding Opportunity Announcement (FOA) will support replication,
fine-mapping, and sequencing studies of human genomic regions that are
putatively associated with common complex traits, primarily those identified by
genome-wide association studies (GWAS). The purpose is to accelerate the discovery of causal genes and genetic variants that influence
diseases and disorders within the NIAMS mission, and improve our understanding
of the molecular mechanisms of disease. These studies are expected to be
undertaken in existing cohorts in which phenotypic
data have already been collected; thus, this FOA will not support recruitment,
clinical characterization of subjects, studies using animal models, or
discovery GWAS efforts. Awards under this FOA will provide support for personnel, genotyping, sequencing, analyses and other costs, as
justified by the study design.

Background

A GWAS is defined as
any study of genetic variation across the entire human genome that is designed
to identify genetic associations with observable traits, or the presence or absence of a disease or condition. The genome-wide
association approach has proven to be powerful in systematically identifying
common genetic variants of modest effect that influence the risk of many
complex diseases. There are many areas of the NIAMS
mission (http://www.niams.nih.gov/About_Us/Mission_and_Purpose/long_range.asp)
in which GWAS could furnish novel insights; and some significant advances have
already been made in rheumatoid arthritis, systemic lupus erythematosus (SLE),
psoriasis and osteoporosis, as a result of GWAS.

While the potential of
GWAS to identify risk loci in complex diseases is becoming evident, it is clear
that many challenges lie ahead. The NIAMS has considered the resources required
for success, and has put in place an FOA that
supports genome-wide association analyses that make use of existing
genotype/phenotype datasets
(https://grants.nih.gov/grants/guide/pa-files/PAR-08-123.html).

Recently, a roundtable
discussion convened extramural investigators from across
NIAMS mission areas to assess GWAS challenges and opportunities. Participants
pointed out that while GWAS in a number of areas have yielded promising
results, follow-up studies are needed to translate initial findings of GWAS
into the biological insights that could lead to
predictive, diagnostic, and therapeutic advances. For instance, in the initial
analysis of a GWAS, many of the observed associations may be false positives.
Thus, it is necessary to conduct replication studies to discern the true positives, typically by testing a subset of the most strongly
associated single nucleotide polymorphisms (SNPs) or other genetic variants in
one or more additional populations of samples. In addition, in the regions of
confirmed associations, the causal variants will only
occasionally be among those that are directly genotyped. Moreover, GWAS detect
almost exclusively the effects of common SNPs, but offer limited power to
capture any rare variants (<1% population frequency) and structural
variants, such as insertions, deletions, copy number
variants, microsatellites, segmental duplications, transposons, and inversions.
Detailed sequencing may be necessary to characterize the genetic variations in
the disease-associated regions, and enhance the identification of disease causal variants.

Objectives

This FOA will provide
support for replication, fine-mapping, and sequencing studies of the genomic
regions found through GWAS that have the potential to identify genes and
genetic variants that influence the risk for rheumatic, musculoskeletal, and skin diseases. For this FOA, the term
replication is defined as testing a subset of the most strongly associated
SNPs or other genetic variants in one or more additional study populations. The
term fine-mapping is defined as additional
genotyping of SNPs or other genetic variants, which have not been included in
the original genotyping platform, near a gene or a region that has been
replicated for association with a disease or trait. Diseases of interest
include, but are not limited to: rheumatoid
arthritis, systemic lupus erythematosus, ankylosing spondyloarthritis, gout,
scleroderma, psoriasis, vitiligo, alopecia areata, osteoporosis, and
osteoarthritis. An application may propose, for example, a replication study
alone, or a replication study plus fine-mapping and
sequencing efforts, or fine-mapping plus sequencing studies. These follow-up
studies are needed to validate the initial associations revealed from GWAS,
narrow the association intervals of interest, identify genes and genetic variants associated with disease, and extend the
findings to diverse populations (different races, ethnicities, or environmental
exposures) and related phenotypes. Well-designed replication studies should
follow the published guidelines (NCI-NHGRI Working
Group on Replication in Association Studies, Nature 447, 655-660, 2007) for
what constitutes replication of a genotype-phenotype association and how it can
be best achieved.

Applicants are expected
to have access to DNA collections, phenotypic and
genotypic data, or exposure data from existing cohorts of sufficient size at
the time of submission, in order to adequately address the specific aims.
Applicants who plan to seek data from the NIH GWAS data repository will be
expected to follow the published guidance
(https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-013.html).
Specifically, applicants should anticipate the need to submit a data access
request and a Data Use Certification that is co-signed by the investigator and
the designated Institutional Official. In the
Approach section of the Research Strategy, the applicants should
briefly address plans for requesting access to data and state their intention
to abide by the Data Use Certification. Applicants who intend to access data in the NIH GWAS data repository for the
research proposed are advised to secure that access prior to submitting their
application for NIH support.

Applications are
expected to reflect the inclusion of appropriate expertise such as collaborative groups of clinicians, geneticists, statisticians,
and bioinformaticians, in order to ensure that the complexities of phenotypic
definition, the study design, and statistical genetic analysis are adequately
considered. Each application should clearly define
the rationale for the proposed replication, fine-mapping, and sequencing
studies, provide detailed information or a sufficient summary of the GWAS that
identified the genomic regions associated with a particular disease or trait,
and explain why those regions should be assigned
priority for a replication study, or fine-mapping and sequencing effort. For a
replication study, the application should also clearly describe the study
population chosen for replication, in comparison with the initial discovery cohort, any known replication effort(s), either
published, in progress, or planned, and the statistical power of the
replication sample set to detect a smaller genetic effect than reported in the
original study, in order to address potential publication
bias. For sequencing and fine-mapping studies, applications should also
describe the rationale for the proposed study design, including the extent and
scope of resequencing efforts, efficient fine-mapping strategies, the choice of
statistical methods for data analysis, and the costs
associated with sequencing and genotyping. The investigators are encouraged to
seek resources for high quality and cost effective sequencing and
genotyping.

Applications responding to this FOA may seek support for,
but not limited to:

Specimen preparation
and transfer;

Sequencing effort for
identification of SNP and other genetic variants;

Genotyping of selected
genetic polymorphisms;

Data analyses; and

Appropriate support for
the Principal Investigator and other key personnel
(this part of requested budget is expected to be modest).

This
FOA will use theNIH
Research Project Grant (R01)award mechanism.The Project
Director/Principal Investigator (PD/PI) will be solely responsible for
planning, directing, and executing the proposed project.

In some
instances, an active NIAMS R01 award may currently support a GWAS with a two-stage design, including initial discovery and
replication. In such instances, investigators may submit a revision (formerly
competing supplement) application in response to this FOA, to support
additional replication, fine-mapping, or sequencing efforts,
provided the application conforms to both the budgetary requirements of this
FOA and the format requirements of revision applications.

This
FOA uses Just-in-Time information concepts (see SF424 (R&R) Application Guide). It also uses the modular,
as well as the non-modular, budget formats (seehttps://grants.nih.gov/grants/funding/modular/modular.htm).
Specifically, a U.S. organization submitting an application with direct costs
in each year of $250,000 or less (excluding consortium Facilities and
Administrative [F&A] costs) should use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all
foreign applicants must complete and submit budget requests using the Research
& Related Budget component.

2.
Funds Available

Because the nature and
scope of the proposed research will vary from application to application, it is
anticipated that the size and duration of each award will also vary. Although
the financial plans of the IC(s) provide support for this program, awards
pursuant to this funding opportunity are contingent upon the availability of
funds.

The NIAMS intends to commit
approximately $1.5 million total costs in each of fiscal years 2010, 2011 and
2012, to fund three to four projects per year. Applications may request direct
costs up to $250,000 per year and project duration of up to two years.

Facilities
and Administrative (F&A) costs requested by consortium participants are not
included in the direct cost limitation, see NOT-OD-05-004.

The decision of whether to
apply for a grant with a single PD/PI or multiple PDs/PIs grant is the
responsibility of the investigators and applicant organizations and should be
determined by the scientific goals of the project. Applications for grants with
multiple PDs/PIs will require additional information, as outlined in the
instructions below. When considering the multiple PD/PI option,
please be aware that the structure and governance of the PD/PI leadership team
as well as the knowledge, skills and experience of the individual PDs/PIs will
be factored into the assessment of the overall scientific merit of the
application. Multiple PDs/PIs on a project share the authority and responsibility
for leading and directing the project, intellectually and
logistically.Each PD/PI is responsible and accountable to the grantee
organization, or, as appropriate, to a collaborating organization, for the
proper conduct of the project or program, including the submission of required
reports. For further information on multiple PDs/PIs, please seehttps://grants.nih.gov/grants/multi_pi.

Number
of Applications. Applicants may submit more than one application,
provided that each application is scientifically distinct.

Resubmissions. Applicants may submit a resubmission application, but
such application must include an Introduction addressing the previous peer
review critique (Summary Statement).Beginning with applications intended
for the January 25, 2009 official submission due date, all original new
applications (i.e., never submitted) and competing renewal applications will be
permitted addressing
the previous peer review critique (Summary Statement) in only a single amendment (A1). See https://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-003.html and NOT-OD-09-016. Original
new and competing renewal applications that were submitted prior to January 25,
2009 will be permitted two amendments (A1 and A2). For these
grandfathered applications, NIH expects that any A2 will be submitted no
later than January 7, 2011, and NIH will not accept A2 applications after that
date.

In some
instances, an active NIAMS R01 award may currently support a GWAS with a
two-stage design, including initial discovery and replication. In such
instances, investigators may submit a revision (formerly competing
supplement) application in response to this FOA, to
support additional replication, fine-mapping or sequencing effort, provided the
application conforms to both the budgetary requirements of this FOA and the
format requirements of revision applications.

Renewals. Renewal (formerly
competing continuation) applications will not be accepted for this FOA.

Section IV. Application and Submission Information

To
download a SF424 (R&R) Application Package and SF424 (R&R) Application
Guide for completing the SF424 (R&R) forms for this FOA, use the Apply for
Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow
the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

The individual(s) designated as
PDs/PIs on the application must be registered also in the NIH eRA Commons.In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned
the PI role in the eRA Commons prior to the submission of the application.

Each PD/PI must
hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization
Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a
PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist
under one Commons account.

When multiple PDs/PIs are
proposed, all PDs/PIs at the applicant organization must be affiliated with
that organization.PDs/PIs located at another institution need not be
affiliated with the applicant organization, but must be affiliated with their
own organization to be able to access the Commons.

This registration/affiliation must
be done by the AOR/SO or his/her designee who is already registered in the Commons.

Both the PD(s)/PI(s)
and AOR/SO need separate accounts in the NIH eRA Commons since both are
authorized to view the application image.

Several of the steps of the registration
process could take four weeks or more. Therefore, applicants should immediately
check with their business official to determine whether their
organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept
electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application Information

Applicants must
download the SF424 (R&R) application forms and the SF424 (R&R)
Application Guide for this FOA through Grants.gov/Apply.

Note:
Only the forms package directly attached to a specific FOA can be used. You
will not be able to use any other SF424 (R&R) forms (e.g., sample forms,
forms from another FOA), although some of the "Attachment" files may
be useable for more than one FOA.

Prepare all
applications using the SF424 (R&R) application forms and in accordance with
the SF424 (R&R) Application Guide for this FOA
through Grants.gov/Apply.

The SF424 (R&R)
Application Guide is critical to submitting a complete and accurate application
to NIH. Some fields within the SF424 (R&R) application components, although
not marked as mandatory, are required by NIH (e.g., the Credential log-in
field of the Research & Related Senior/Key Person Profile component must
contain the PD/PIs assigned eRA Commons User ID). Agency-specific
instructions for such fields are clearly identified in the Application Guide.
For additional information, see Frequently Asked Questions Application
Guide, Electronic
Submission of Grant Applications.

The SF424 (R&R) application
has several components. Some components are required, others are optional. The
forms package associated with this FOA in Grants.gov/APPLYincludes all applicable components, required and optional. A completed
application in response to this FOA includes the data in the following
components:

Proposed research should provide special
opportunities for furthering research programs through the use of unusual
talent, resources, populations, or environmental conditions in other countries
that are not readily available in the United States
(U.S.) or that augment existing U.S. resources.

SPECIAL
INSTRUCTIONS

Applications with
Multiple PDs/PIs

When multiple PDs/PIs
are proposed, NIH requires one PD/PI to be designated as the "Contact PI,
who will be responsible for all communication between the PDs/PIs and the NIH,
for assembling the application materials outlined below, and for coordinating
progress reports for the project. The contact PD/PI must meet all eligibility
requirements for PD/PI status in the same way as other PDs/PIs, but has no
other special roles or responsibilities within the project team beyond those
mentioned above.

Information for the
Contact PD/PI should be entered in Item 13 of the SF424 (R&R) Cover
component.All other PDs/PIs should be listed in the Research &
Related Senior/Key Person component and assigned the project role of
PD/PI.Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission.The Commons ID of each PD/PI must be included
in the Credential field of the Research & Related Senior/Key Person
component.Failure to include this data field will cause the application
to be rejected.

All projects proposing Multiple PDs/PIs will
be required to include a new section describing the leadership plan approach
for the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the research plan, entitled Multiple PD/PI Leadership Plan, must be
included. A rationale for choosing a multiple PD/PI approach should be
described. The governance and organizational structure of the leadership team
and the research project should be described, and should include communication
plans, process for making decisions on scientific direction, and procedures for
resolving conflicts.The roles and administrative, technical, and
scientific responsibilities for the project or program should be delineated for
the PDs/PIs and other collaborators.

If budget allocation
is planned, the distribution of resources to specific components of the project
or the individual PDs/PIs should be delineated in the Leadership Plan. In the
event of an award, the requested allocations may be reflected in a footnote on the
Notice of Award (NoA).

Applications
Involving a Single Institution

When all PDs/PIs are
within a single institution, follow the instructions contained in the SF424
(R&R) Application Guide.

Applications
Involving Multiple Institutions

When multiple institutions
are involved, one institution must be designated as the prime institution and
funding for the other institution(s) must be requested via a subcontract to be
administered by the prime institution. When submitting a detailed budget, the
prime institution should submit its budget using the Research & Related
Budget component.All other institutions should have their individual
budgets attached separately to the Research & Related Subaward Budget
Attachment(s) Form.See Section 4.8 of the SF424 (R&R) Application
Guide for further instruction regarding the use of the subaward budget
form.

When submitting a
modular budget, the prime institution completes the PHS398 Modular Budget
component only.Information concerning the consortium/subcontract budget
is provided in the budget justification. Separate budgets for each
consortium/subcontract grantee are not required when using the Modular budget
format. See Section 3.4 of the Application Guide for further instruction
regarding the use of the PHS398 Modular Budget component.

Prospective
applicants are asked to submit a letter of intent that includes the following
information:

Descriptive title of proposed research.

Name, address, and telephone number of
the PD(s)/PI(s).

Names of other key personnel.

Participating institutions.

Number and title of this funding
opportunity.

Although
a letter of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains allows IC
staff to estimate the potential review workload and plan the review.

Applications may be submitted on or after the opening date and must be successfully
received by Grants.gov no later than 5:00 p.m. local
time(of the applicant
institution/organization) on the application due date(s). (See Section
IV.3.A. for
all dates.) If
an application is not submitted by the due date(s) and time, the application
may be delayed in the review process or not reviewed. All applications must meet the following criteria to be considered on-time:

All registrations must be complete prior to the submission deadline

The application must receive a Grants.gov tracking number and timestamp (or eRA help desk ticket confirming a system issue preventing submission) by 5:00 p.m. local time on the submission deadline date.

Any system identified errors/warnings must be corrected and the submission process completed within the error correction window.

Submission to Grants.gov is not the last step - applicants must follow their application through to the eRA Commons to check for errors and warnings and view their assembled application!

3.C.2 Two Day Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond.
As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See
NOT-OD-10-123.

Once an application
package has been successfully submitted through Grants.gov NIH provides applicants a two day error correction window to correct any eRA identified errors or warnings before a final assembled application is created in the eRA Commons. The standard error correction window is two (2) business days, beginning the day after the submission deadline and excluding weekends and standard federal holidays. All errors must be corrected to successfully complete the submission process. Warnings will not prevent the application from completing the submission process.

Note that the following caveats apply:

Initial application submission must be on-time.

The AOR/institutions is expected to enforce that application changes made within the error correction window are restricted to those necessary to address system-identified errors/warnings. NIH may reject any application that includes additional changes.

Proof of on-time submission (e.g., Grants.gov timestamp and tracking number) and description of all changes made within the window must be documented in the PHS 398 Cover Letter component of the application.

3.C.3 Viewing an Application in the eRA Commons

Once any eRA identified errors have been addressed and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further processing.

If
everything is acceptable, no further action is necessary. The application will
automatically move forward for processing by the Division of Receipt and
Referral, Center for Scientific Review, NIH, after two business days, excluding
Federal holidays.

Prior
to the submission deadline, the AOR/SO can Reject the assembled application
and submit a changed/corrected application within the two-day viewing window.
This option should be used if the AOR/SO determines that warnings should be
addressed or if information was lost or compromised during transmission.
Reminder: warnings do not stop further application processing. If an
application submission results in warnings (but no errors), it will
automatically move forward after two business days if no action is taken.
Please remember that some warnings may not be applicable or may need to be
addressed after application submission.

If
the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or did not
transfer correctly during the submission process). The AOR/SO should first
contact the eRA Commons Helpdesk to confirm the system error,
document the issue, and determine the best course of action. NIH will not
penalize the applicant for an eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to Reject the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH late policy guidelines and may not be accepted. The reason for
this delay should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two days.

Upon
receipt, applications will be evaluated for completeness by the Center for
Scientific Review, NIH. Incomplete applications will not be reviewed.

All NIH awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award
costs are allowable. A grantee may, at its own risk and without NIH prior
approval, incur obligations and expenditures to cover costs up to 90 days
before the beginning date of the initial budget period of a new or renewal
award if such costs: 1) are necessary to conduct the project, and 2) would be
allowable under the grant, if awarded, without NIH prior approval. If specific
expenditures would otherwise require prior approval, the grantee must obtain
NIH approval before incurring the cost. NIH prior approval is required for any
costs to be incurred more than 90 days before the beginning date of the initial
budget period of a new or renewal award.

The incurrence
of pre-award costs in anticipation of a competing or non-competing award
imposes no obligation on NIH either to make the award or to increase the amount
of the approved budget if an award is made for less than the amount anticipated
and is inadequate to cover the pre-award costs incurred. NIH expects the
grantee to be fully aware that pre-award costs result in borrowing against
future support and that such borrowing must not impair the grantee's ability to
accomplish the project objectives in the approved time frame or in any way
adversely affect the conduct of the project. See NIH Grants Policy Statement https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements and Information.

PD/PI Credential (e.g., Agency
Login)

The
NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the PROFILE
Project Director/Principal Investigator section, Credential log-in field
of the Research & Related Senior/Key Person Profile component.

Organizational DUNS

The
applicant organization must include its DUNS number in its Organization Profile
in the eRA Commons. This DUNS number must match the DUNS number provided at CCR
registration with Grants.gov. For
additional information, see Frequently Asked Questions Application Guide, Electronic Submission
of Grant Applications.

PHS398 Research Plan Component
Sections

Application Research Strategy Length: The R01
application Research Plan component of the PHS398 (Item 3) may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts.

Do not use the Appendix to circumvent the page limitations. An application that does not comply with the required page
limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH
considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value and further the
advancement of the research. When resources have been developed with NIH funds
and the associated research findings published or provided to NIH, it is
important that they be made readily available for research purposes to
qualified individuals within the scientific community. If the final data/resources are not amenable to sharing,
this must be explained in the Resource Sharing section of the application (see https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(b) Sharing Model Organisms:
Regardless of the amount requested, all applications where the development of
model organisms is anticipated are expectedto include a
description of a specific plan for sharing and distributing unique model
organisms and related resources or state appropriate reasons why such sharing
is restricted or not possible (see Sharing
Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a
genome-wide association study are expected to provide a plan for
submission of GWAS data to the NIH-designatedGWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. A genome-wide association study is defined as
any study of genetic variation across the entire genome that is designed to
identify genetic associations with observable traits (e.g., blood pressure or
weight) or the presence or absence of a disease or condition. For further
information see Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and https://grants.nih.gov/grants/gwas/.)

Foreign Applications
(Non-domestic [non-U.S.] Entities)

Indicate how the proposed project has specific
relevance to the mission and objectives of the NIH/IC and has the potential for
significantly advancing the health sciences in the United States.

Section V. Application Review
Information

1.
Criteria

Only
the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are
complete will be evaluated for scientific and technical merit by an appropriate
peer review group convened by CSR and in accordance with NIH peer review
procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below

As
part of the scientific peer review, all applications will:

Undergo
a selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned an impact/priority score;

Receive
a written critique; and

Receive
a second level of review by the appropriate national
advisory council or board.

Applications
submitted in response to this funding opportunity will compete for available
funds with all other recommended applications. The following will be
considered in making funding decisions:

Scientific
and technical merit of the proposed project as determined by scientific
peer review.

Availability
of funds.

Relevance
of the proposed project to program priorities.

The mission
of the NIH is to support science in pursuit of knowledge about the biology and
behavior of living systems and to apply that knowledge to extend healthy life
and reduce the burdens of illness and disability. As part of this
mission, applications submitted to the NIH for grants or cooperative agreements
to support biomedical and behavioral research are evaluated for scientific and
technical merit through the NIH peer review system.

Overall
Impact. Reviewers will provide an overall impact/priority score
to reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in
consideration of the following five core review criteria, and additional review
criteria (as applicable for the project proposed).

Core Review
Criteria. Reviewers will consider each of the five
review criteria below in the determination of scientific and technical merit,
and give a separate score for each. An application does not need to be
strong in all categories to be judged likely to have major scientific
impact. For example, a project that by its nature is not innovative may
be essential to advance a field.

Significance. Does the
project address an important problem or a critical barrier to progress in the
field? If the aims of the project are achieved, how will scientific
knowledge, technical capability, and/or clinical practice be improved?
How will successful completion of the aims change the concepts, methods,
technologies, treatments, services, or preventative interventions that drive
this field?

Investigator(s). Are the
PD/PIs, collaborators, and other researchers well suited to the project?
If Early Stage Investigators or New Investigators, do they have appropriate
experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If
the project is collaborative or multi-PD/PI, do the investigators have
complementary and integrated expertise; are their leadership approach, governance
and organizational structure appropriate for the project?

Innovation. Does the
application challenge and seek to shift current research or clinical practice
paradigms by utilizing novel theoretical concepts, approaches or methodologies,
instrumentation, or interventions? Are the concepts, approaches or
methodologies, instrumentation, or interventions novel to one field of research
or novel in a broad sense? Is a refinement, improvement, or new
application of theoretical concepts, approaches or methodologies,
instrumentation, or interventions proposed?Specific to this FOA:
What advantages does the project offer for replication, fine-mapping and
sequencing studies of genetic regions putatively associated with the complex
trait(s) under investigation? What advantages does the study offer for
discriminating true positive results from the large number of false positive
results expected with GWAS? What advantages does it offer for follow-up studies
to identify causative genetic variants and develop diagnostic, preventive, or
therapeutic strategies?

Approach. Are the
overall strategy, methodology, and analyses well-reasoned and appropriate to
accomplish the specific aims of the project? Are potential problems,
alternative strategies, and benchmarks for success presented? If
the project is in the early stages of development, will the strategy establish
feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) Protections for Human Subjects, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?Specific
to this FOA: Are the study design and population chosen well described and
appropriate for the aims proposed? Have any potential biases in subject
selection been identified, and is the approach for minimizing these biases
appropriate? Are environmental factors and other covariates that might influence
the phenotype also available for analysis? Are the phenotype and exposure
measures of sufficient quality and completeness to provide maximum scientific
value from the addition of targeted genotyping?

Environment. Will the
scientific environment in which the work will be done contribute to the
probability of success? Are the institutional support, equipment and
other physical resources available to the investigators adequate for the
project proposed? Will the project benefit from unique features of the
scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project
proposed, reviewers will consider the following additional items in the
determination of scientific and technical merit, but will not give separate
scores for these items.

Protections for Human Subjects. For
research that involves human subjects but does not involve one of the six
categories of research that are exempt under 45 CFR Part 46, the committee will
evaluate the justification for involvement of human subjects and the proposed
protections from research risk relating to their participation according to the
following five review criteria: 1) risk to subjects, 2) adequacy of protection
against risks, 3) potential benefits to the subjects and others, 4) importance
of the knowledge to be gained, and 5) data and safety monitoring for clinical
trials.

For research that involves human subjects and meets
the criteria for one or more of the six categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate: 1) the justification for the
exemption, 2) human subjects involvement and characteristics, and 3) sources of
materials.

Inclusion of Women, Minorities, and Children.
When the proposed project involves clinical research, the committee will
evaluate the proposed plans for inclusion of minorities and members of both
genders, as well as the inclusion of children.

Vertebrate Animals. The committee
will evaluate the involvement of live vertebrate animals as part of the
scientific assessment according to the following five points: 1) proposed use of
the animals, and species, strains, ages, sex, and numbers to be used; 2)
justifications for the use of animals and for the appropriateness of the species
and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting
discomfort, distress, pain and injury to that which is unavoidable in the
conduct of scientifically sound research including the use of analgesic,
anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and
5) methods of euthanasia and reason for selection if not consistent with the
AVMA Guidelines on Euthanasia.

Resubmission Applications. When
reviewing a Resubmission application (formerly called an amended application),
the committee will evaluate the application as now presented, taking into
consideration the responses to comments from the previous scientific review
group and changes made to the project.

Renewal Applications. When reviewing
a Renewal application (formerly called a competing continuation application),
the committee will consider the progress made in the last funding period.

Revision Applications. When
reviewing a Revision application (formerly called a competing supplement
application), the committee will consider the appropriateness of the proposed
expansion of the scope of the project. If the Revision application relates to a
specific line of investigation presented in the original application that was
not recommended for approval by the committee, then the committee will consider
whether the responses to comments from the previous scientific review group are
adequate and whether substantial changes are clearly evident.

Biohazards. Reviewers will assess
whether materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Additional Review Considerations

As applicable for
the project proposed, reviewers will address each of the following items, but
will not give scores for these items and should not consider them in providing
an overall impact/priority score.

Budget
and Period Support. Reviewers will
consider whether the budget and the requested period of support are fully
justified and reasonable in relation to the proposed research.

Select Agents Research. Reviewers will assess the information
provided in this section of the application, including 1) the Select Agent(s)
to be used in the proposed research, 2) the registration status of all entities
where Select Agent(s) will be used, 3) the procedures that will be used to
monitor possession use and transfer of Select Agent(s), and 4) plans for
appropriate biosafety, biocontainment, and security of the Select Agent(s).

Applications
from Foreign Organizations.
Reviewers will assess whether the project presents special opportunities for
furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions that exist in other countries and
either are not readily available in the United States or augment existing U.S. resources.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section
IV.5., Funding Restrictions.

A final progress report, invention statement,
and Financial Status Report are required when an award is relinquished when a
recipient changes institutions or when an award is terminated.

Section
VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research (program), peer review, and financial or
grants management issues:

Human Subjects
Protection:Federal regulations (45 CFR 46) require that applications
and proposals involving human subjects must be evaluated with reference to the
risks to the subjects, the adequacy of protection against these risks, the
potential benefits of the research to the subjects and others, and the
importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety
Monitoring Plan:Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (Phase I); efficacy studies (Phase II);
efficacy, effectiveness and comparative trials (Phase III). Monitoring should
be commensurate with risk. The establishment of data and safety monitoring
boards (DSMBs) is required for multi-site clinical trials involving
interventions that entail potential risks to the participants (NIH Policy for
Data and Safety Monitoring, NIH Guide for Grants and Contracts, https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing
Research Data:Investigators
submitting an NIH application seeking $500,000 or more in direct costs in any
single year are expected to include a plan for data sharing or state why this
is not possible (https://grants.nih.gov/grants/policy/data_sharing).Investigators should
seek guidance from their institutions, on issues related to institutional
policies and local institutional review board (IRB) rules, as well as local,
State and Federal laws and regulations, including the Privacy Rule. Reviewers
will consider the data sharing plan but will not factor the plan into the determination
of the scientific merit or the impact/priority score.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see https://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see https://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement. Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Inclusion of Women, Minorities, and Children:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them.

Required Education on the Protection of Human Subject
Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy,investigators
funded by the NIH must submit or have submitted for them to the
National Library of Medicines PubMed Central (see http://www.pubmedcentral.nih.gov/), an
electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no
later than 12 months after the official date of publication. The
NIH Public Access Policy is available at (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html).For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable
Health Information:The Department
of Health and Human Services (HHS) issued final modification to the
"Standards for Privacy of Individually Identifiable Health
Information", the "Privacy Rule", on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance Portability and
Accountability Act (HIPAA) of 1996 that governs the protection of individually
identifiable health information, and is administered and enforced by the HHS
Office for Civil Rights (OCR).

Decisions about
applicability and implementation of the Privacy Rule reside with the researcher
and his/her institution. The OCR website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs
in NIH Grant Applications or Appendices:
All applications and proposals
for NIH funding must be self-contained within specified page limitations. For
publications listed in the appendix and/or Progress report, Internet addresses
(URLs) or PubMed Central (PMC) submission identification numbers must be used
for publicly accessible on-line journal articles.Publicly accessible
on-line journal articles or PMC articles/manuscripts accepted for publication
that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference
in either the Bibliography & References Cited section, the Progress Report
Publication List section, or the Biographical Sketch section of the NIH grant
application. A URL or PMC submission identification number citation may be
repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.

Authority and
Regulations:This program is described in
the Catalog
of Federal Domestic Assistance athttp://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372. Awards are made
under the authorization of Sections 301 and 405 of the Public Health Service
Act as amended (42 USC 241 and 284) and under Federal
Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject
to the terms and conditions, cost principles, and other considerations
described in the NIH Grants
Policy Statement.

The PHS strongly
encourages all grant recipients to provide a smoke-free workplace and
discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

Loan
Repayment Programs:NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical, pediatric,
contraception, infertility, and health disparities related areas. The LRP is an
important component of NIH's efforts to recruit and retain the next generation
of researchers by providing the means for developing a research career
unfettered by the burden of student loan debt. Note that an NIH grant is not
required for eligibility and concurrent career award and LRP applications are
encouraged. The periods of career award and LRP award may overlap providing the
LRP recipient with the required commitment of time and effort, as LRP awardees
must commit at least 50% of their time (at least 20 hours per week based on a
40 hour week) for two years to the research. For further information, please
see: http://www.lrp.nih.gov/.